Kilohertz Transcranial Magnetic Perturbation (kTMP): A New Non-invasive Method to Modulate Cortical Excitability

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Abstract Background Non-invasive brain stimulation (NIBS) provides a method for safely perturbing brain activity, and has been employed in basic research to test hypotheses concerning brain-behavior relationships with increasing translational applications. Objective We introduce and evaluate a novel subthreshold NIBS method: kilohertz transcranial magnetic perturbation (kTMP). KTMP is a magnetic induction method that delivers continuous kHz-frequency cortical electric fields which may be amplitude-modulated to potentially mimic electrical activity at endogenous frequencies. Methods We used TMS to compare the amplitude of motor-evoked potentials (MEPs) in a hand muscle before and after kTMP. In Experiment 1, we applied kTMP for 10 min over motor cortex to induce an E-field amplitude of approximately 2.0 V/m, comparing the effects of waveforms at frequencies of 2.0, 3.5, or 5.0 kHz. In Experiments 2 and 3 we used two forms of amplitude-modulated kTMP with a carrier frequency at 3.5 kHz and modulation frequencies of either 20 or 140 Hz. Results The only percept associated with kTMP was an auditory tone, making kTMP amenable for double-blind experimentation. Relative to sham stimulation, non-modulated kTMP at 2.0 and 3.5 kHz resulted in an increase in cortical excitability, with Experiments 2 and 3 providing a replication of this effect for the 3.5 kHz condition. Although amplitude-modulated kTMP increased MEP amplitude compared to sham, no enhancement was found compared to non-modulated kTMP. Conclusions kTMP opens a new experimental NIBS space inducing relatively large amplitude subthreshold E-fields able to increase cortical excitability with minimal sensation.

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